Fullerene, which is a carbon cluster represented by C60, is a novel carbon allotrope discovered by Smally, Kroto et al. in 1985. Since a large-scale synthetic method was established in 1990, studies have dramatically progressed in both basic and application fields.
At first, fullerenes were thought to have low chemical reactivity, however, it was shown that various anionic substrates are easily added thereto as an electron deficient olefin. In addition, Diels-Alder reaction, 1,3-dipolar cyclo addition reaction or the like proceeds well to give an adduct attached to the double bond of a conjunction region of 6-membered ring and 6-membered ring of a fullerene.
An effect of such a chemically active novel substance group on a living organism also attracts the interest. For example, with regard to a fullerene derivative, an HIV protease inhibitory activity has been reported for the compound of the following formula (non-patent document 1).
In this situation, a research on a fullerene derivative further having a new bioactivity has been desired, however, in fact, an investigation for application as a bioactive agent has not so much progressed.
Therefore, the inventor of this application synthesized two types of C60 fullerene derivatives represented by the following formulae (1) and (2):
and has investigated their bioactivities. These derivatives have a characteristic that they easily dissolve in an organic solvent (such as DMSO), which is miscible in water, and can be used for a reaction in an aqueous solution.
The inventor first focused on the inhibition of hepatitis C virus RNA polymerase and the inhibition of HIV reverse transcriptase in the process of this investigation.
Hepatitis C virus (HCV) infects through the blood or the like and causes chronic hepatitis. The infected patients are more likely to develop liver cirrhosis or liver cancer, and the natural recovery rate is extremely low. The current therapeutic method is administration of interferon, which is sometimes further combined with ribavirin. However, the elimination rate of HCV is about one-third, which is low. Therefore, development of a new anti-HCV drug has been awaited.
HCV is an RNA virus. After it invades human liver cells, it produces several enzymes from its own RNA by using the protein synthesis system of the host (human) cells. One of these enzymes is HCV RNA polymerase, which is essential for growth of HCV.
It has been reported that if the activity of this RNA polymerase is inhibited, growth of hepatitis C virus can be inhibited, and the virus itself can be eliminated.
On the other hand, AIDS was first reported in 1981, and since then, it has been spread all over the world, which has become a serious social problem. This AIDS is a disease in which the immune system of the body breaks down due to the human immunodeficiency virus (HIV), therefore the patients are susceptible to a variety of infectious diseases and lead to death. HIV is similar to hepatitis C virus and is an RNA virus.
The agents currently used as an AIDS therapeutic drug can be classified into two main categories. One is an inhibitor of the reverse transcriptase that synthesizes DNA from the RNA of HIV, and the other is an inhibitor of the enzyme necessary for growth of HIV (HIV protease, an enzyme that converts a protein synthesized from the virus RNA into an enzyme having an activity). As a reverse transcriptase inhibitor, a nucleoside analogue is mainly used, however, it has a disadvantage in that it is also toxic to human cells. Also, there are few protease inhibitors which are stable in vivo and whose activities are high. In this way, there is no specific drug for AIDS in the present circumstances, and furthermore, the fact that HIV acquires resistance against these drugs has become a big problem.
In this circumstance, as mentioned above, it has been reported that a fullerene derivative has an HIV protease inhibitory activity. At present, various derivatives other than this have been attempted, however, a fullerene derivative having an inhibitory activity against HIV reverse transcriptase has not been reported.    Non-patent document 1: R. F. Schinazi, et al., Antimicrob. Agents Chemother, 37, 1707 (1993)